The long term goal of the proposed research is to develop novel magnetic resonance spectroscopy (MRS) data acquisition techniques, capable to identify and monitor patients affected by mild cognitive impairment (MCI). MCI is generally defined as a transitional state between normal aging and dementia, and is currently diagnosed through extensive neuropsychological testing. A hallmark characteristic of this transitional state is an early change in the brain biochemistry, which can be non-invasively detected through 1H MRS techniques. Such techniques also have the potential to provide faster, more efficient treatment monitoring in MCI and disease detection prior to the onset of memory impairment symptoms. We will carefully optimize 1H MRS data acquisition techniques, to accurately measure two metabolites whose concentrations are reported to change in MCI: myo-Inositol (mI) -a marker of glial cell numbers- and N-acetyl aspartate (NAA)-a marker of neuronal integrity. Through simulations, we will tailor pulse sequences to acquire simplified in vivo spectra, by filtering out metabolites reported to be constant in the disease, while maintaining the two metabolites of interest in the spectrum. We hypothesize that simpler spectra will leave less room for error while quantifying data through fitting, therefore allowing increased measurement reproducibility and the detection of smaller changes that can be attributed to disease or treatment. We will implement the most successful pulse sequences on a 3T clinical scanner, and perform in vitro experiments to validate the improved measurement reproducibility for the metabolites of interest. Through a comprehensive partnership between GE Global Research and Albany Medical Center, we will also compare the sensitivities of the newly developed methods in separating a cohort of MCI patients from a cohort of age-matched normal controls. Tailoring pulse sequences for accurate NAA and mI detection may significantly improving MCI diagnosis and monitoring. Decreased disease diagnosis costs, as well as more efficient monitoring of disease, leading to lower clinical trial costs involving MCI patients, can be obtained as a consequence of this study. Moreover, the direct results of this study, i.e., metabolite tailored pulse sequences, have the potential to benefit detection and monitoring of other diseases, in which up- or down- regulation of NAA or mI are reported including multiple sclerosis, acute brain injury, or hepatic encephalopathy. [unreadable] [unreadable] [unreadable]